Impaired locomotion and dopamine signaling in retinoid receptor mutant mice.
In the adult mouse, single and compound null mutations in the genes for retinoic acid receptor beta and retinoid X receptors beta and gamma resulted in locomotor defects related to dysfunction of the mesolimbic dopamine signaling pathway. Expression of the D1 and D2 receptors for dopamine was reduced in the ventral striatum of mutant mice, and the response of double null mutant mice to cocaine, which affects dopamine signaling in the mesolimbic system, was blunted. Thus, retinoid receptors are involved in the regulation of brain functions, and retinoic acid signaling defects may contribute to pathologies such as Parkinson's disease and schizophrenia.
Krezel
W
W
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université Louis Pasteur, Collège de France, Boite Postale 163, 67404 Illkirch Cedex, France.
Ghyselinck
N
N
Samad
T A
TA
Dupé
V
V
Kastner
P
P
Borrelli
E
E
Chambon
P
P
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D019281:Dimerization; D004298:Dopamine / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology; D017933:Peripheral Nervous System / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D047488:Retinoid X Receptors; D012559:Schizophrenia / Q000209:etiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C082925:retinoic acid receptor beta; D003042:Cocaine; D004298:Dopamine